Our major objectives are to examine cell replication as well as cellular response to DNA damage as a function of aging, in vitro in cultured human cells and in vivo in rat & mouse cell populations. Examination of phytohemagglutinin (PHA) stimulated human peripheral lymphocytes with the BrdU-differential chromatid staining techniques demonstrated that the decline in PHA response with aging was due to both a decline in the number of cells stimulated to replicate by PHA as well as a decline in the replication rate of the stimulated cells. Investigations of the effect of aging on SCE induction resulted in the following findings: 1) SCE induction in vivo by several structurally distinct compounds was diminished with aging, 2) SCE induction was decreased in post-embryonic development complementing the decline seen in aging, 3) Impairment of immune response as measured by mitogen responsiveness correlated well with the decline in SCE induction and 4) Spontaneous SCE induction does not appear to be altered with in vitro passage (in vitro aging). In vivo sister chromatid exchange analysis was applied to the in utero detection of SCE as well as to the use of this system to assess cancer chemotherapeutic agents.